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Brain Networks in Subjective Cognitive Decline and Mild Cognitive Impairment: Characterizing the Predementia Stages Using Magnetoencephalography

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Brain Networks in Subjective Cognitive Decline and Mild Cognitive Impairment: Characterizing the Predementia Stages Using Magnetoencephalography UNIVERSIDAD COMPLUTENSE DE MADRID FACULTAD DE PSICOLOGÍA TESIS DOCTORAL Brain networks in subjective cognitive decline and mild cognitive impairment: characterizing the predementia stages using magnetoencephalography Redes cerebrales en quejas subjetivas de memoria y deterioro cognitivo leve: caracterización de las etapas de pre-demencia mediante magnetoencefalografía MEMORIA PARA OPTAR AL GRADO DE DOCTOR PRESENTADA POR David López Sanz DIRECTORES Fernando Maestú Unturbe Pilar Garcés López Francisco de Vicente Pérez Madrid, 2018 © David López Sanz, 2018 UNIVERSIDAD COMPLUTENSE DE MADRID FACULTAD DE PSICOLOGÍA TESIS DOCTORAL Brain networks in subjective cognitive decline and mild cognitive impairment: characterizing the predementia stages using magnetoencephalography Redes cerebrales en quejas subjetivas de memoria y deterioro cognitivo leve: caracterización de las etapas de pre-demencia mediante magnetoencefalografía MEMORIA PARA OPTAR AL GRADO DE DOCTOR PRESENTADA POR David López Sanz Directores Fernando Maestú Unturbe Pilar Garcés López Francisco de Vicente Pérez Madrid, 2018 A mi familia: mi padre, mi madre y mi hermana. Porque aunque suene a tópico, sin vuestra ayuda y apoyo a lo largo de toda mi vida nunca habría podido escribir estas palabras. Gracias por haberme apoyado siempre y haberme dado la oportunidad de estudiar durante tantos años sin ninguna presión añadida. Gracias por haber estado a mi lado en los momentos más duros, cuando los caprichos de la vida decidieron que las cosas serían un poco más difíciles, por no haberme dejado caer en ningún momento de aquel aciago año. Gracias por último, y más importante, a Silvia, A TI. Gracias por haber sido mi motor durante todos estos años, porque soportaste a mi lado cada adversidad e hiciste que cada buen momento, fuese aún mejor al compartirlo contigo. Gracias por darme estabilidad, por ayudarme a digerir y a no desmotivarme en cada noche de “ahora no sale nada”. Por aceptar y compartir conmigo este camino que he decidido recorrer, a pesar de la inestabilidad y la incertidumbre, sin cuestionarlo jamás. Porque eres y serás parte fundamental de todo esto: antes, durante y después. Acronyms Aβ Beta-amyloid AD Alzheimer´s Disease aDMN Anterior default mode network AEC Amplitude envelope correlation APA American Psychiatric Association APP Amyloid precursor protein BEM Boundary element method BOLD Blood Oxygenation Level Dependent CAT Computerized axial tomography CO Cingulo-opercular network DAN Dorsal attentional network DCL Deterioro Cognitivo Leve DMN Default mode network DTI Diffusion tensor imaging ECoG Electrocorticography EEG Electroencephalography EKG Electrocardiogram EOG Electrooculogram FC Functional connectivity FDG F-2-fluoro-2-deoxy-D-Glucose fMRI Functional magnetic resonance imaging FPN Fronto-parietal network HC Healthy control HPI Head position information Hz Hertz ICA Independent component analysis iEEG Intracranial electroencephalography IWG International Working Group MCI Mild cognitive impairment MEG Magnetoencephalography MMSE Mini Mental State Examination MNI Montreal neurological institute MRI Magnetic resonance imaging NIA-AA National institute on aging and the Alzheimer´s Association PCC Posterior cingulate cortex pDMN Posterior default mode network PiB Pittsburgh compound B PLV Phase locking value QSM Quejas Subjetivas de Memoria RSN Resting state network SQUID Superconducting quantum interference device SSS Signal Space Separation T Tesla Contents Agradecimientos Acronyms Contents List of tables List of figures Resumen Abstract 1. General introduction ............................................................................. 9 1.1. Introduction to neuroimaging ......................................................... 9 1.1.1. Structural imaging techniques ............................................... 11 1.1.2. Functional imaging techniques .............................................. 15 1.1.3. Brain oscillations and resting state ........................................ 19 1.2. Dementia and Alzheimer´s Disease ............................................... 29 1.2.1. Dementia: definition and subtypes ........................................ 29 1.2.2. Neuropsychological changes in AD ........................................ 34 1.2.3. Neurobiological basis of AD ................................................... 34 1.2.4. Risk factors for AD .................................................................. 37 1.2.5. Socioeconomic impact of AD ................................................. 40 1.2.6. Mild cognitive Impairment ..................................................... 41 1.2.7. Subjective Cognitive Decline .................................................. 43 1.3. Introduction to thesis methods ..................................................... 47 1.3.1. MEG components ................................................................... 47 1.3.2. MEG recording description .................................................... 48 1.3.3. Preprocessing pipeline ........................................................... 50 1.3.4. Source space reconstruction .................................................. 53 1.3.5. Main analyses ......................................................................... 54 2. General objectives .............................................................................. 61 3. Experiment 1 Spectral analysis in SCD and MCI .................................. 63 3.1. Summary of objectives .................................................................. 64 3.2. Abstract ......................................................................................... 65 3.3. Introduction .................................................................................. 66 3.4. Materials and methods ................................................................. 68 3.4.1. Subjects .................................................................................. 68 3.4.2. Diagnostic criteria .................................................................. 68 3.4.3. MEG recordings ...................................................................... 70 3.4.4. MRI acquisition ....................................................................... 71 3.4.5. MEG Signal preprocessing ...................................................... 71 3.4.6. Source reconstruction ............................................................ 71 3.4.7. Spectral analysis ..................................................................... 72 3.4.8. Statistical analysis .................................................................. 73 3.5. Results ........................................................................................... 74 3.5.1. Neuropsychological assessment ............................................ 74 3.5.2. Differences in hippocampal volume ...................................... 74 3.5.3. Differences in alpha peak frequency...................................... 74 3.5.4. Differences in alpha relative power ....................................... 76 3.5.5. Multiple linear regressions ..................................................... 76 3.6. Discussion ...................................................................................... 78 3.7. Summary of conclusions ............................................................... 83 3.8. References ..................................................................................... 85 4. Experiment 2 Connectivity analysis in SCD and MCI ........................... 91 4.1. Summary of objectives .................................................................. 92 4.2. Abstract ......................................................................................... 94 4.3. Introduction .................................................................................. 95 4.4. Materials and methods ................................................................. 96 4.4.1. Subjects .................................................................................. 96 4.4.2. Diagnostic criteria .................................................................. 97 4.4.3. MEG recordings ...................................................................... 98 4.4.4. MEG Signal preprocessing ...................................................... 99 4.4.5. MRI acquisition ....................................................................... 99 4.4.6. Source reconstruction .......................................................... 100 4.4.7. Connectivity analysis ............................................................ 100 4.4.8. Network calculation ............................................................. 101 4.4.9. Statistical analysis ................................................................ 102 4.5. Results ......................................................................................... 103 4.5.1. Connectivity values .............................................................. 103 4.5.2. Differences in RSN ................................................................ 106 4.5.3. Correlation of beamformer weights .................................... 106 4.5.4. Differences in hippocampal volume .................................... 106 4.5.5. Correlation analyses ............................................................. 107 4.6. Discussion .................................................................................... 107 4.7. Experiment 2 appendix ..............................................................
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